How transcription factors drive choice of the T cell fate
H Hosokawa, EV Rothenberg - Nature Reviews Immunology, 2021 - nature.com
H Hosokawa, EV Rothenberg
Nature Reviews Immunology, 2021•nature.comRecent evidence has elucidated how multipotent blood progenitors transform their identities
in the thymus and undergo commitment to become T cells. Together with environmental
signals, a core group of transcription factors have essential roles in this process by directly
activating and repressing specific genes. Many of these transcription factors also function in
later T cell development, but control different genes. Here, we review how these transcription
factors work to change the activities of specific genomic loci during early intrathymic …
in the thymus and undergo commitment to become T cells. Together with environmental
signals, a core group of transcription factors have essential roles in this process by directly
activating and repressing specific genes. Many of these transcription factors also function in
later T cell development, but control different genes. Here, we review how these transcription
factors work to change the activities of specific genomic loci during early intrathymic …
Abstract
Recent evidence has elucidated how multipotent blood progenitors transform their identities in the thymus and undergo commitment to become T cells. Together with environmental signals, a core group of transcription factors have essential roles in this process by directly activating and repressing specific genes. Many of these transcription factors also function in later T cell development, but control different genes. Here, we review how these transcription factors work to change the activities of specific genomic loci during early intrathymic development to establish T cell lineage identity. We introduce the key regulators and highlight newly emergent insights into the rules that govern their actions. Whole-genome deep sequencing-based analysis has revealed unexpectedly rich relationships between inherited epigenetic states, transcription factor–DNA binding affinity thresholds and influences of given transcription factors on the activities of other factors in the same cells. Together, these mechanisms determine T cell identity and make the lineage choice irreversible.
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